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Evidence that the M2 membrane-spanning region lines the ion channel pore of the nicotinic receptor

Leonard, Reid J. and Labarca, Cesar G. and Charnet, Pierre and Davidson, Norman and Lester, Henry A. (1988) Evidence that the M2 membrane-spanning region lines the ion channel pore of the nicotinic receptor. Science, 242 (4885). pp. 1578-1581. ISSN 0036-8075. http://resolver.caltech.edu/CaltechAUTHORS:20150128-145454703

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Abstract

Site-directed mutagenesis and expression in Xenopus oocytes were used to study acetylcholine receptors in which serine residues (i) were replaced by alanines (alpha, delta subunits) or (ii) replaced a phenylalanine (beta subunit) at a postulated polar site within the M2 transmembrane helix. As the number of serines decreased, there were decreases in the residence time and consequently the equilibrium binding affinity of QX-222, a quaternary ammonium anesthetic derivative thought to bind within the open channel. Receptors with three serine-to-alanine mutations also displayed a selective decrease in outward single-channel currents. Both the direction of this rectification and the voltage dependence of QX-222 blockade suggest that the residues mutated are within the aqueous pore of the receptor and near its cytoplasmic (inner) surface.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1126/science.2462281DOIArticle
http://www.sciencemag.org/content/242/4885/1578PublisherArticle
http://www.jstor.org/stable/1702380JSTORArticle
ORCID:
AuthorORCID
Lester, Henry A.0000-0002-5470-5255
Additional Information:© 1988 American Association for the Advancement of Science. 30 June 1988; Accepted 11 October 1988. We thank M. Fearey and A. Charnet for help with the oocytes, L. Czyzyk for expert technical help with the mutagenesis, and G. Eisenman for discussion. This research was supported by grants from NIH (NS-11756) and the Muscular Dystrophy Association of America and by postdoctoral fellowships to R.J.L. (NS-8083) and to P.C. (Bourse Lavoisier and FRM, France).
Funders:
Funding AgencyGrant Number
NIHNS-11756
Muscular Dystrophy AssociationUNSPECIFIED
NIHNS-8083
Bourse LavoisierUNSPECIFIED
Fondation pour la Recherche MédicaleUNSPECIFIED
Record Number:CaltechAUTHORS:20150128-145454703
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20150128-145454703
Official Citation:Leonard, R., Labarca, C., Charnet, P., Davidson, N., & Lester, H. (1988). Evidence that the M2 membrane-spanning region lines the ion channel pore of the nicotinic receptor. Science, 242(4885), 1578-1581. doi: 10.1126/science.2462281
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:54199
Collection:CaltechAUTHORS
Deposited By: Joanne McCole
Deposited On:28 Jan 2015 23:35
Last Modified:08 Nov 2017 23:53

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